tbuckley/cabot-search huggingface dataset:
Racial disparities in DLBCL: Analysis of SEER data from 2010-2019.
Authors: Soyon Lee, John D. Seeger
Journal: Journal of Clinical Oncology (2023)

e18552 Background: Diffuse large B-cell lymphoma (DLBCL) is among the most common subtype of non-Hodgkin’s lymphoma accounting 31% of new cases. Introduction of immunotherapy and cell-based gene therapy has transformed the treatment landscape, yet there continue to be health disparities including differences in treatments received and health outcomes according to socioeconomic status. We aimed to quantify the association between race (white, black, American Indian/Alaska Native, Asian or Pacific Islander [API]) and cancer-specific survival among DLBCL patients. Methods: A retrospective observational study was conducted using the National Cancer Institute’s 2000-2019 Surveillance, Epidemiology, and End Results (SEER) Research Plus Data, 17 registries database. The SEER registry collects data on cancer incidence, patient and disease characteristics, and survival from approximately 35% of the US population. Patients were excluded if they had non-primary DLBCL or missing data. Survival analyses were used to evaluate cancer-specific mortality among 4 racial groups (white, black, American Indian/Alaska Native, API). Cox proportional hazards regression was used to assess the difference in cancer-specific mortality across race groups adjusting for age, sex, marital status, income, rurality, and Ann Arbor Stage. Results: The analytic sample included adult US patients diagnosed with DLBCL from 2010 to 2015 (N = 25,495). Of these 25,495 patients with DLBCL, the majority were White (82.8%), followed by API (9.3%), Black (7.4%), and American Indian/Alaska Native (0.5%). Age at diagnosis, sex, marital status, income differed across race groups. The crude cancer-specific mortality for blacks at year 2 was 29%, while 25% for whites, 24% for American Indians/Alaska Natives, and 29% for API. At year 6, the cancer-specific mortality was 36% for blacks, 33% for whites, 33% for American Indians/Alaska Natives, 35% for API. However, accounting for differences in patient characteristics (adjusting for age, sex, marital status, income, rurality, and Ann Arbor stage) resulted in an increased hazard risk (HR) of cancer-specific mortality for Black and Asian compared to whites (HR 1.28; 95% CI 1.18 to 1.40; and HR 1.19; 95% 1.11 to 1.29, respectively). The HR of cancer-specific mortality comparing American Indian/Alaska Natives to whites was 1.00; 95% CI .73 to 1.38, with the wide confidence intervals indicating that sample size is limited for this comparison. Conclusions: Despite advances in new treatment options, differences in cancer-specific mortality exists between different race groups among patients with DLBCL. The study highlights various sociodemographic features at diagnosis that could reflect disparities and lead to differences in cancer-specific mortality across race groups. It may be feasible to address some of the observed differences at DLBCL diagnosis and this may translate to better outcomes among patients with DLBCL.
Association between bispecific T cell engager (BiTE) therapy and inflammatory adverse effects (AEs) in patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Michael Xu, Brandon Wummer, William Kevin Kelly, Babar Bashir
Journal: Journal of Clinical Oncology (2023)

e14534 Background: Cancer immunotherapies have offered limited efficacy in treating mCRPC. A novel class of immunotherapy are BiTEs, which target both a specific cancer antigen and CD3 to enhance T cell anti-tumor activity. Although BiTEs are a promising avenue for cancer research, their safety profiles are not well-understood. Thus far, it is known that first-in-class blinatumomab is associated with AEs such as cytokine release syndrome, neurotoxicity, and febrile neutropenia. Given their mechanism of action and possible propensity to produce a general inflammatory environment, we aimed to explore the systemic and inflammatory AEs of BiTEs in mCRPC patients. Methods: A retrospective chart review was performed on an IRB-approved database. Inclusion criteria included a history of mCRPC and BiTE therapy. There were no exclusion criteria. Study objectives were to evaluate whether BiTE therapy led to de novo inflammatory AEs or exacerbation of pre-existing inflammatory disorders. AEs were defined/graded as immune system disorders per Common Terminology Criteria for Adverse Effects v5.0. Results: 24 mCRPC patients in our clinic received at least 1 dose of BiTE therapy. Mean (range) age was 67.3 (54-79) years. 5 (20.8%) had pre-existing inflammatory disorders. Mean (range) treatment course was 14 (0-44) weeks. 6 (25.0%) discontinued due to inflammatory AEs, 15 (62.5%) discontinued due to disease progression, 1 (4.2%) discontinued due to noncompliance, and 2 (8.4%) are currently on BiTE therapy. Notable de novo AEs included arthralgia (8.4%), thrombophlebitis (8.4%), myocarditis (4.2%), giant cell arteritis (4.2%), and pneumonitis (4.2%). Patients with pre-existing inflammatory conditions (5/5) were statistically more likely to develop inflammatory AEs after BiTE therapy initiation compared to those without (4/19) (p &lt; 0.01). Of the 9 patients who developed inflammatory AEs, 6 (66.7%) developed inflammatory AEs after the first dose of BiTE therapy. After the first dose, mean C-reactive protein was significantly elevated in patients with pre-existing inflammatory conditions (10.0) compared to those without (1.6) (p = 0.041). Conclusions: Our analysis suggests that BiTE therapies are associated with inflammatory AEs other than cytokine release syndrome, neurotoxicity, and febrile neutropenia. In particular, some of our patients developed vasculitis, myocarditis, or pneumonitis. Furthermore, patients with pre-existing inflammatory conditions are at significantly greater risk of developing inflammatory AEs compared to patients without pre-existing inflammatory conditions. Thus, patients with pre-existing inflammatory conditions who are receiving BiTE therapy should be cautiously observed. Additional data from larger BiTE therapy clinical trials is needed to further support these findings.
Malignant glomus tumor of the head and neck: A National Cancer Database analysis.
Authors: Quinton Anderson, Beau Hsia, Jaylin Tuman, Xinxin Wu, Erin Sinai, Peter T. Silberstein, Darby Keirns
Journal: Journal of Clinical Oncology (2023)

e18078 Background: Malignant glomus tumors of the head and neck are rare malignancies originating from glomus bodies found within the skin, soft tissues, and mucosa of the head and neck. Malignant glomus tumors often arise from benign glomus tumors and rarely metastasize. In cases where metastasis had ocurred it was typically fatal. Another review of the malignant glomus tumor cases indicated that only a minority developed metastases. These findings, along with a general lack of knowledge regarding demographic and socioeconomic factors on glomus tumors warrants further investigation. The National Cancer Database (NCDB) was analyzed to identify demographic factors among patients and better understand the epidemiology of these tumors. Methods: A retrospective cohort analysis was performed using the 2004–2020 National Cancer Database including patients with a histologically confirmed malignant glomus tumor diagnosis (N = 42). Demographic factors such as race, age, sex, Hispanic status, insurance status, Charlson-Deyo score, facility type, and distance to facility were analyzed by descriptive statistics. Results: A total of 42 patients with a confirmed malignant glomus tumor diagnosis were identified in the National Cancer Database (NCDB) between 2004 – 2020. The average age of diagnosis was 60.9 years (SD = 13.7, range = 36 - 90 years). The aortic body and other paraganglia were the most common primary tumor sites (57.1%). Most patients were White (69.0%) or Black (28.6%). Most individuals (88.1%) had a Charlson-Deyo comorbidity score of 0. A higher percentage of patients were in the bottom quartile of income earners (31.4%). Fewer patients lived in metropolitan counties with populations less than 1 million compared to those that lived in counties with a population greater than 1 million (52.5%). More patients were privately insured (47.6%) relative to those who were insured by Medicare/Medicaid or uninsured. The most common treatment facility type was an academic/research program (57.5%) and patients lived an average of 40.1 miles (SD = 65.6, range = 0.6 – 265.4) from their treatment facility. Conclusions: Before this study, there had been no previous report on the socioeconomic profile of patients with malignant glomus tumors. However, our findings indicate that these patients are more prone to having a low income and that White patients are more likely to be affected. No obvious connection exists between metastases and racial minority status. Additional research is needed to grasp how socioeconomic factors, such as low income and minority status, affect the risk, diagnosis, treatment, and overall survival of individuals with malignant glomus tumors.
The impact of COVID-19 on mortality, length of stay, and cost of care among patients with gastrointestinal malignancies: A propensity score-matched analysis.
Authors: Mark Bilinyi Ulanja, Bryce D. Beutler, Samuel B Governor, Kwabena Oppong Asafo-Agyei, Samuel Edusa, Daniel Antwi-Amoabeng, Reginald N. Ulanja, Millicent Amankwah, Vijay Neelam, Tarig Mabrouk, Ganiyu A. Rahman, Francis T. Djankpa, Olatunji B. Alese
Journal: Journal of Clinical Oncology (2023)

e15510 Background: The SARS-CoV-2 (COVID-19) pandemic has had a lasting impact on the care of cancer patients. Multiple studies have shown that individuals with cancer are at high risk of serious complications in the setting of COVID-19 infection, but the impact in patients with gastrointestinal (GI) malignancies remain incompletely understood. We aimed to assess the impact of COVID-19 infection on mortality, length of stay (LOS), and cost of care among patients with GI malignancies, and identify differences in outcomes based on primary tumor site. Methods: We analyzed discharge encounters collected from the National Inpatient Sample (NIS) between March 2020 and December 2020, using propensity score-matching (PSM), and COVID- 19 as treatment effect. Results: Of the 87,684 patient discharges with GI malignancies, 1,892 were positive for COVID-19 (C+ve) and eligible for matching in the PSM model. Proportion for C+ve; male (61.2%), female (38.8%), White (55.8%), Black (17.9%), Hispanic (18.6%) and other (7.6%). Median age was 69 years (1QR: 61-77). Monthly variation reflected the wave and plateau dynamics of the spread of COVID-19. Following PSM analysis, C+ve patients with GI tumors demonstrated increased mortality compared to their COVID-19-negative (C-ve) counterparts (21.3% versus 11.9%, p &lt; 0.001). C+ve patients with colorectal cancer (CRC) had significantly higher mortality compared to those who were C-ve; 39.95% [161/403] versus 24% [54/225], p = 0.035). In addition, C+ve patients with GI tumors had a longer LOS (9.42 days versus 6.95 days, p &lt; 0.001) and increased cost of care ($26,048.29 versus $21,625.24, p = 0.001) compared to C-ve. Higher odds of mortality from myocardial infarction among C+ve(OR = 3.54, P = 0.001) while mortality due to pulmonary embolism or liver failure was not significantly different between C+ve and C-ve groups. Conclusions: This PSM analysis suggests that prior to the introduction of vaccines, C+ve patients with GI tumors faced approximately double the odds of mortality, an increased LOS of 2.5 days, and increased cost of care of about $4,400 compared to their C-ve counterparts. The disparity of outcomes was most pronounced among CRC patients. It is possible that the direct effects of the SARS-CoV-2 virus on the GI tract may predispose to mortality and disease severity, warranting further investigation. [Table: see text]
Initial results of dose finding in a first-in-human phase 1 study of a novel Claudin 6 (CLDN6) targeted antibody drug conjugate (ADC) TORL-1-23 in patients with advanced solid tumors.
Authors: Gottfried E. Konecny, Andrea Elisabeth Wahner Hendrickson, Boris Winterhoff, Cinthiya Chander, Sanela Bilic, Simon Davenport, Adrine Chung, Lei-Lani Miller, Michael F. Press, Stephen P. Letrent, Dennis J. Slamon
Journal: Journal of Clinical Oncology (2023)

3082 Background: CLDN6, a member of the claudin family of tight junction proteins, is expressed at high levels in multiple human malignancies and has little to no expression in normal tissues. This expression profile makes CLDN6 an ideal target for development of new therapeutics. TORL-1-23 is first-in-class ADC targeting the tumor-specific antigen CLDN6. Methods: TORL123-001 (NCT05103683) is an ongoing, 2-part, first in human study to characterize the safety, tolerability, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended phase 2 dose (RP2D) of TORL-1-23 monotherapy in participants with advanced solid tumors. Serum pharmacokinetics (PK), immunogenicity and clinical efficacy are also assessed. TORL-1-23 is administered as a 30-minute IV infusion once every 3 weeks in 21-day cycles. During Part 1 (Dose Escalation), cohorts of 1 to 6 participants are evaluated at each dose level according to an accelerated titration design. In Part 2 (Dose Expansion), several cohorts of patients with CLDN6-expressing cancers will be evaluated to confirm the RP2D in ovarian cancer, NSCLC, and other CLDN6-expressing cancers using a CLDN6 IHC companion diagnostic. Results: As of 01FEB2023, 22 patients with ovarian (n=18), testicular (n=3), and endometrial (n=1) cancers were enrolled and treated across 8 dose levels ranging from 0.2 to 2.4 mg/kg IV every 3 weeks. 95% of pts had received ≥ 3 prior lines of treatment in the metastatic setting. The most common treatment-related adverse events were Gr1/2 fatigue (n=5), Gr1 peripheral neuropathy (n=4), and Gr1 nausea (n=3). No DLTs have been reported and no dose reductions have been required. Preliminary PK data demonstrate sustained exposure of TORL-1-23 ADC over the 21 day dosing interval and low levels of serum MMAE indicating low off-target MMAE exposure outside of tumor. Partial responses (PR) were observed in 4/17 efficacy evaluable participants with CLDN6+ disease (3 ovarian, 1 testicular). Dose escalation is ongoing and updated results will be presented. Conclusions: TORL-1-23 has a favorable safety/tolerability profile and PK characteristics with preliminary antitumor activity in pts with heavily-pretreated CLDN6-expressing ovarian and testicular cancers. Doses above the historic MTD for MMAE containing ADCs may be explored given the safety/tolerability and PK data observed up to 2.4 mg/kg. Dose finding is ongoing to identify the MTD and optimal doses for subsequent development. Clinical trial information: NCT05103683 .
Outcomes with bevacizumab for radiation induced-brain necrosis.
Authors: Meri Muminovic, Carlos Carracedo Uribe, Shivani Dalal, Ignacio Castellon, Aaron Falchook, Olger Nano, Luis E. Raez
Journal: Journal of Clinical Oncology (2023)

e14006 Background: Radiation necrosis (RN) is post-radiation complication that leads to increased permeability and disruption of the blood brain barrier (BBB). This in turn leads to a pro-inflammatory state and an increased production of vascular-endothelial growth factor (VEGF). Bevacizumab is a monoclonal antibody against VEGF and is a potential treatment for RN. The objective of the study is to assess effectiveness of bevacizumab (BEV) for the treatment of brain RN in adults. Methods: Retrospective chart review of 22 patients with various solid malignancies including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), metastatic melanoma and breast cancer with clinical or radiographic diagnosis of RN seen at Memorial Cancer Institute (MCI) in a 3-year period, from January 1 st , 2019 to January 1 st , 2023. Radiation doses ranged from 18-24 Gy (single fraction) or 24-27 Gy (3-fraction) for radiosurgery and 30-37.5 Gy for whole brain radiotherapy. Patients were identified that developed RN and VEGF inhibitors were subsequently given to assess effectiveness in the treatment of the condition. We evaluated the dose, frequency, number of treatments received, adverse effects and therapeutic benefits of BEV. Therapeutic benefit was defined as patients that received bevacizumab had a radiological and clinical improvement of the RN (clinical benefit). Brain imaging with MRI or PET/CT scan was completed both pre and post treatment to evaluate efficacy of treatment. Patients were initially given 4 cycles with a subsequent 4 more cycles if it was beneficial and tolerated treatment. Results: 22 patients were included in the study, 9 were males (41%) and median age 66 (range 31-81). 91% (20/22) had a diagnosis of lung cancer. 1 patient had a diagnosis of SCLC, while 19 were diagnosed with NSCLC. The study had a good representation of different races including Non-Hispanic Whites 7 (32%), Hispanics 10 (45%), Blacks 13% (3) and Asians 10% (2). Over 95% (21/22) of patients achieved a clinical benefit, while one patient did not (5%). Patients experienced improvement in cognitive function, headaches, dizziness, weakness, and other symptoms with BEV. MRIs showed improvement in edema and a reduction/stabilization of brain lesions. The most frequent dosing regimen used was BEV 10 mg/kg every two weeks. The median number of cycles given was 4 cycles (1-12). The most common adverse events were hypertension, minor nose bleeding, an occasional protein found in urine. There were no severe AEs or discontinuation of therapy with bevacizumab. Conclusions: This study demonstrated treatment with BEV 10 mg/kg every two weeks for a total of 12 cycles is well tolerated and has potential clinical benefit in RN in lung cancer patients with CNS metastasis. The therapeutic effects of VEGF inhibitors were seen in our small population study but warrants further investigation in a larger population study.
Excess testing after diagnosis of incidental pulmonary nodules (IPNs) in the Medicare population.
Authors: Raymond U. Osarogiagbon, Paul Pinsky
Journal: Journal of Clinical Oncology (2023)

e18922 Background: Management of IPNs re-distributes lung cancer to earlier stages at diagnosis, but most people with IPNs will not develop lung cancer. We assessed the rate of diagnostic procedures related to suspected lung cancer in people on Medicare who had IPNs. Methods: We analyzed the 5% SEER-Medicare database for IPNs, diagnostic procedures, and lung cancer status. We analyzed two cohorts: persons with chest CT scan procedure codes accompanied by ICD-9 code 793.11 or ICD-10 code R91.1 during 2014-2017 (IPN cohort) and persons with CT scan procedure codes without the IPN codes during that period (control cohort). We computed rates of lung cancer-related diagnostic procedures (per 100 person-years [PY]) during the 2-year follow-up period, including chest CT, PET/PET-CT, bronchoscopy, needle biopsy, and surgical procedures. We used multivariable Poisson regression to estimate procedure rate ratios (RRs) across cohorts, controlling for demographics and COPD status. Using the regression RRs, we estimated excess procedures in the IPN cohort over the 2-year follow-up period by subtracting the control cohort (background) rate. Based on prior data on the reduced proportion (by 36%) of late-stage disease associated with follow-up of IPNs, we computed a metric of excess procedures per late-stage case avoided by IPN follow-up. Results: Of 19,009 (IPN) and 60,985 (control) persons, 3.6% and 0.8%, respectively, had lung cancer diagnosed during 2-year follow-up. Among IPN cohort without lung cancer, rates per 100 PY were 73.1, 9.4, 4.0, 3.2 and 1.0 for chest CT, PET/PET-CT, bronchoscopy, needle biopsy, and surgical procedures, respectively (Table). Poisson regression showed significantly elevated RRs for the IPN versus control cohort for all procedures, with RRs ranging from 1.27 (bronchoscopy) to 2.03 (Chest CT). Excess procedures in the IPN cohort (per 100 persons) ranged from 63 for chest CT to 0.9 for surgical procedures (Table). Excess procedures per late-stage case avoided ranged from 48 for chest CT to 0.7 for surgical procedures. Conclusions: The burden of diagnostic procedures following reported IPNs is modest relative to the yield of early-stage lung cancer. [Table: see text]
Plasma proteomics approach to distinguishing PD-1 inhibitor-associated myocarditis from acute myocardial infarction in patients receiving PD-1 inhibitors treatment: A clinical and preclinical study.
Authors: Yuxi Luo, Yali Yi, Zhiqin Lu, Anwen Liu, Zhimin Zeng
Journal: Journal of Clinical Oncology (2023)

e14698 Background: Immune checkpoint inhibitor (ICI)-related myocarditis is a rare but severe side effect that requires attention to distinguish it from other cardiovascular emergencies. Therefore, new biomarkers are needed for the early diagnosis of ICI-related myocarditis, especially to distinguish it from other cardiovascular emergencies. Our study aims to explore plasma biomarkers with high specificity and sensitivity using proteomic analysis for the early diagnosis of ICI-related myocarditis and to distinguish it from acute myocardial infarction (AMI). Methods: Patients with ICI-related myocarditis and AMI were selected and matched for potential confounding effects such as age, gender, smoking history, and chronic heart diseases. A label-free liquid chromatography-mass spectrometry (LC-MS) proteomics approach was used to analyze plasma samples and screen sensitive and specific myocarditis protein biomarkers. Further validation will be performed at the level of patients and animal models of ICI-related myocarditis and AMI. Results: We performed plasma proteomics on 15 plasma samples from 5 pairs of samples with PD-1 inhibitor-associated myocarditis at baseline (control group) and diagnosis (myocarditis group) and 5 cases of acute myocardial infarction (MI group) confirmed by coronary angiography in the Second Affiliated Hospital of Nanchang University. In total, we identified a total of 1521 plasma proteins and 1325 quantifiable plasma proteins across all 15 plasma samples. Further analysis of the differential proteins showed that 34 proteins with significantly differentially expressed in myocarditis group samples compared with other groups. Among them, several proteins were significantly up-regulated (MYOM3, TNNC1, MYL1, MYOM2, CA3, MYLPF, ECI1, LGALS1, PSMA7, PSMB3, PSMA4, PSMB6, CKM, ABCB6, UGP2, ALDOA, TPM2) or down-regulated (MAN1A1, SPTB, YTHDC2, CLEC11A, GSN, APOA4) in myocarditis samples. Compared with the other groups, the ICI-related myocarditis group showed molecular changes in myocardial contraction, proteasome, immunoregulation, NF-κB signaling pathway, arginine and proline metabolism, and cysteine and methionine metabolism. We then performed ELISA on additional ICI-related myocarditis and AMI patients and corresponding animal models. The Troponin C, Myom 3, UGP2, and Galectin-1 proteins related to immune or inflammation were significantly increased. Conclusions: Our study has revealed that proteins related to the immune system or inflammation may be sensitive and specific plasma biomarkers for identifying ICI-related myocarditis. However, further large sample cohorts are needed to confirm these findings.